Is PRG4 p.Ser388Pro (c.1162T>C) pathogenic?

PRG4 p.Ser388Pro (c.1162T>C) is classified Uncertain significance in PRG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-19). AlphaMissense: likely benign (0.0837); Ultra-rare (popmax 0.0248%, amr); Associated with Inborn genetic diseases.

What condition is associated with PRG4 p.Ser388Pro (c.1162T>C)?

PRG4 p.Ser388Pro (c.1162T>C) is associated with Inborn genetic diseases (ClinVar).

How common is PRG4 p.Ser388Pro (c.1162T>C) in the general population?

PRG4 p.Ser388Pro (c.1162T>C) is ultra-rare (popmax 0.0248%, amr) (gnomAD).

What do computational predictors say about PRG4 p.Ser388Pro (c.1162T>C)?

AlphaMissense predicts likely benign (score 0.0837) — an in-silico prediction, not a clinical call.

PRG4 p.Ser388Pro

c.1162T>C · rs750005482 · VCV3218615

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0837 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0248%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0837	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Regional constraint	o/e 0.95	unconstrained · MANE · 10 kb · p 0.3 · regional, not allelic
Overall
CADD	0.499	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0248% Admixed American · 11/44,386 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0107%

Overall 0.00172% 24/1,399,320 alleles · ultra-rare exomes 12/1,345,916 · genomes 12/53,404 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0248%	4,035
East Asian	0.0154%	6,492
African / African-American	0.0071%	14,085
Ashkenazi Jewishnot grpmax-eligible	0.00446%	22,426
Finnishnot grpmax-eligible	0.00398%	25,115
European (non-Finnish)	0.000188%	532,093

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRG4
Protein: p.Ser388Pro
Coding: c.1162T>C
MANE Select: NM_005807
dbSNP: rs750005482
Type: single nucleotide variant
Location: chr1:186306881 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.76
Residue 388: the 'disordered' region; the '59 x 8 aa repeats of k-x-p-x-p-t-t-x' region

Full PRG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRG4 p.Ala1246Val Uncertain significance ★★ ⚠ same condition
PRG4 p.Asp87Asn Uncertain significance ★★ ⚠ same condition
PRG4 p.Lys287Arg Uncertain significance ★★ ⚠ same condition
PRG4 p.Pro409Leu Uncertain significance ★★ ⚠ same condition
PRG4 p.Val1399Phe Uncertain significance ★★ ⚠ same condition
PRG4 p.Ala641Thr Likely benign ★★ same condition
PRG4 p.Glu403Lys Likely benign ★★ same condition
PRG4 p.Leu648= Likely benign ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/prg4-p-ser388pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown